Zika E Glycan Loop Region and Guillain-Barré Syndrome-Related Proteins: A Possible Molecular Mimicry to Be Taken in Account for Vaccine Development.

Grégorie Lebeau,Etienne Frumence,Jean-Jacques Hoarau,Jonathan Turpin,Pascale Krejbich-Trotot,Floran Begue,Gilles Gadea,Wildriss Viranaicken,Philippe Desprès

doi:10.3390/vaccines9030283

Abstract

The neurological complications of infection by the mosquito-borne Zika virus (ZIKV) include Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuritis. GBS was first associated with recent ZIKV epidemics caused by the emergence of the ZIKV Asian lineage in South Pacific. Here, we hypothesize that ZIKV-associated GBS relates to a molecular mimicry between viral envelope E (E) protein and neural proteins involved in GBS. The analysis of the ZIKV epidemic strains showed that the glycan loop (GL) region of the E protein includes an IVNDT motif which is conserved in voltage-dependent L-type calcium channel subunit alpha-1C (Cav1.2) and Heat Shock 70 kDa protein 12A (HSP70 12A). Both VSCC-alpha 1C and HSP70 12A belong to protein families which have been associated with neurological autoimmune diseases in central nervous system. The purpose of our in silico analysis is to point out that IVNDT motif of ZIKV E-GL region should be taken in consideration for the development of safe and effective anti-Zika vaccines by precluding the possibility of adverse neurologic events including autoimmune diseases such as GBS through a potent mimicry with Heat Shock 70 kDa protein 12A (HSP70 12A).

Highlights

In the last few decades, there has been an increasing number of epidemics associated with mosquito-borne RNA viruses of medical concern such as Dengue Virus (DENV), West Nile Virus (WNV) or Chikungunya Virus [1]
We proposed that amino acids at positions E-152/156/158 of the Zika Virus (ZIKV) epidemic strains might exhibit a molecular mimicry with Guillain–Barré Syndrome (GBS)-related proteins
It seems unlikely that African lineage ZIKV have the ability to mediate GBS since no case was reported to date, which could be an artefact of a poor history of infections

Summary

Introduction

In the last few decades, there has been an increasing number of epidemics associated with mosquito-borne RNA viruses of medical concern such as Dengue Virus (DENV), West Nile Virus (WNV) or Chikungunya Virus [1]. Like DENV and WNV, Zika Virus (ZIKV) belongs to the flavivirus genus of the Flaviviridae family [2]. ZIKV was first reported in Uganda in 1947 in a rhesus monkey; the virus remained silent for years, only provoking sporadic infections until 2007 [2]. The outbreak worldwide spread urged WHO to declare ZIKV as a major public health issue, leading to a global effort to fight against the disease. ZIKV infection causes clinical manifestation in ∼18% of cases ranging from mild disease with a denguelike syndrome, to more severe outcomes such as congenital microcephaly [4,5,6]. Other neurological disorders have been associated with ZIKV infection, including encephalitis, myelitis and, Guillain–Barré Syndrome (GBS) [5,6,7,8]. Uncommon modes of transmission have been described, including sexual and vertical (mother-to-infant) transmission, increasing the threat that this virus represents [9,10,11,12]

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Results

Conclusion